TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19237	57934;57935;57936	chr2:178595645;178595644;178595643	chr2:179460372;179460371;179460370
N2AB	17596	53011;53012;53013	chr2:178595645;178595644;178595643	chr2:179460372;179460371;179460370
N2A	16669	50230;50231;50232	chr2:178595645;178595644;178595643	chr2:179460372;179460371;179460370
N2B	10172	30739;30740;30741	chr2:178595645;178595644;178595643	chr2:179460372;179460371;179460370
Novex-1	10297	31114;31115;31116	chr2:178595645;178595644;178595643	chr2:179460372;179460371;179460370
Novex-2	10364	31315;31316;31317	chr2:178595645;178595644;178595643	chr2:179460372;179460371;179460370
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-27
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.4189
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/R	None	None	0.946	N	0.712	0.45	0.636979074746	gnomAD-4.0.0	6.87372E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02039E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.1284	likely_benign	0.141	benign	-0.425	Destabilizing	0.834	D	0.432	neutral	N	0.503896138	None	None	N
T/C	0.5549	ambiguous	0.5802	pathogenic	-0.245	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
T/D	0.5886	likely_pathogenic	0.6328	pathogenic	0.132	Stabilizing	0.921	D	0.672	neutral	None	None	None	None	N
T/E	0.5457	ambiguous	0.6016	pathogenic	0.049	Stabilizing	0.959	D	0.671	neutral	None	None	None	None	N
T/F	0.5419	ambiguous	0.6207	pathogenic	-0.939	Destabilizing	0.993	D	0.735	prob.delet.	None	None	None	None	N
T/G	0.3286	likely_benign	0.3443	ambiguous	-0.545	Destabilizing	0.769	D	0.616	neutral	None	None	None	None	N
T/H	0.3947	ambiguous	0.4472	ambiguous	-0.877	Destabilizing	0.989	D	0.719	prob.delet.	None	None	None	None	N
T/I	0.5376	ambiguous	0.5815	pathogenic	-0.227	Destabilizing	0.973	D	0.711	prob.delet.	N	0.519020306	None	None	N
T/K	0.4039	ambiguous	0.4739	ambiguous	-0.352	Destabilizing	0.898	D	0.674	neutral	N	0.495930016	None	None	N
T/L	0.2341	likely_benign	0.2727	benign	-0.227	Destabilizing	0.87	D	0.615	neutral	None	None	None	None	N
T/M	0.1471	likely_benign	0.1773	benign	0.042	Stabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
T/N	0.1973	likely_benign	0.2071	benign	-0.127	Destabilizing	0.046	N	0.243	neutral	None	None	None	None	N
T/P	0.4346	ambiguous	0.4486	ambiguous	-0.265	Destabilizing	0.973	D	0.705	prob.neutral	N	0.498255458	None	None	N
T/Q	0.3596	ambiguous	0.4005	ambiguous	-0.395	Destabilizing	0.959	D	0.706	prob.neutral	None	None	None	None	N
T/R	0.3327	likely_benign	0.4227	ambiguous	-0.069	Destabilizing	0.946	D	0.712	prob.delet.	N	0.489505476	None	None	N
T/S	0.1466	likely_benign	0.1574	benign	-0.345	Destabilizing	0.716	D	0.392	neutral	N	0.460603934	None	None	N
T/V	0.3505	ambiguous	0.3825	ambiguous	-0.265	Destabilizing	0.931	D	0.558	neutral	None	None	None	None	N
T/W	0.8115	likely_pathogenic	0.8475	pathogenic	-0.919	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
T/Y	0.5396	ambiguous	0.6011	pathogenic	-0.643	Destabilizing	0.993	D	0.732	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.